5.2- Excretion

what is excretion

The process of removing metabolic waste from cells

functions of the liver

• control of:

  • blood glucose levels

  • amino acid levels

  • lipids levels

• synthesis of:

  • red blood cells in the foetus

  • bile

  • plasma proteins

  • cholesterol

• storage of:

  • iron

  • vitamins

  • glycogen

• breakdown of:

  • hormones

  • red blood cells

breakdown of excess proteins

• body cannot store excess amino acids/proteins that aren’t used in metabolism

• excess amino acids are broken down:

  • deamination

  • ornithine cycle

deamination

• Amine group is converted to ammonia→ goes through ornithine cycle to be converted to urea

• rest of amino acid forms keto acid:

  • enter krebs cycle to be respired

  • converted to lipids or cholesterol

ornithine cycle

• ornithine is an amino acid used to make urea

• process requires input of energy as ATP

detoxification

• liver breaks down substances e.g. alcohol, paracetamol, hydrogen peroxide, insulin

• occurs in SER of hepatocytes

detoxification of ethanol

• ethanol converted to ethanal (acetyl aldehyde)→ catalysed by alcohol dehydrogenase:

  • oxidised NAD→NADH

• Ethanal converted to ethanoate (acetate)→ catalysed by aldehyde dehydrogenase

  • acetate enters krebs cycle

  • oxidised NAD→ NADH

structure of the liver lobules

• several lobules form liver

• hepatic artery supplies oxygenated blood

• hepatic vein carried deox. blood to heart

• hepatic portal vein brings nutrient rich blood from intestines

• bile duct transports bile to gallbladder

sinusoids

• receive blood from hepatic portal vein and hepatic artery

• leaky→ allows small and medium sized proteins to enter and leave blood

• contain Kupffer cells→

  • specialised macrophages- engulf microbes

  • involved in breakdown + recycling of old rbc

• lined by hepatoctyes that have microvilli→ increase SA

bile canniculus

• hepatocytes separated by bile canniculus

• hepatocytes that are close to bile cannuli are rich in golgi vessels→ transport of bile into channels

• cannuli join to form bile duct→ delivers bile to duodenum, diverting through gall bladder

hepatocytes

• in contact with blood in sinusoids

• nuclei distinctly round:

  • some binucleate cells

• active in protein and lipid synthesis→ lots of RER and SER, golgi membranes

• glycogen granules and vesicles contain low density lipoproteins

structure of the kidney

• renal cortex contains bowman’s capsule, convoluted tubules and blood vessels

• renal medulla contains loops of Henle, collecting ducts and blood vessels

• renal pelvis collects urine into the ureters

structure of nephrons

Bowman’s capsule

surrounds capillary ball called glomerulus, from which filtrate is formed

proximal convoluted tubule

reabsorbs useful substances e.g. water, glucose, salts, into surrounding capillaries

Loop of Henle

extends from cortex into medulla and back into cortex and creates high solute gradient in medulla→ helps with reabsorption

Distal convoluted tubule

Fine tunes water balance by reabsorbing water into capillaries

collecting duct

Collects filtrate from multiple nephrons and further fine-tunes water balance

blood vessels in the nephron

• afferent arteriole→ supplies glomerulus with blood

• glomerulus→ fluid forced out of blood within mass of capillaries into Bowman’s capsule through ultrafiltration

• efferent arteriole→ carries blood away from glomerulus

• capillaries around P and DCT and Loop of Henle absorbs salts, glucose, water

ultrafiltration

process by which small molecules e.g. water, glucose, mineral ions and urea are filtered out of the blood and into the bowman’s capsule

process of ultrafiltration

1. blood enters glomerulus through afferent arteriole

2. blood leaves glomerulus via smaller efferent arteriole→ high HS pressure

3. High pressure= molecules forced out of the blood through pores in capillary endothelium

4. molecules move through basement membrane → has collagen fibres that act as selective filter preventing large molecules and blood cells from passing into Bowman’s capsule

5. Molecules move through Bowman’s capsule epithelium→ has podocytes with extensions called pedicels- wrap around capillaries and help filter blood

6. filtered fluid collects in Bowman’s capsule

adaptations of the PCT

• microvilli→ increase SA:V ratio

• basal infoldings→ increase SA:V ratio

• Lots of mitochondria→ provide ATP for Active transport

• co-transporter proteins in plasma membrane→ allow for co-transport of substances

reabsorption in the PCT

1. Na⁺ actively transported into capillaries→ reduced Na⁺ conc. in epithelial cells lining PCT

2. Na⁺ moves from PCT lumen into epithelial cells , down conc. gradient

3. Na⁺ co-transported with substances e.g. glucose, amino acids into epithelial cell

4. reabsorbed molecules can diffuse into blood capillaries

role of the DCT

• makes final adjustments to filtrates content, mainly by reabsorbing water and salts

• involves:

  • alteration of DCT membrane permeability to regulate further absorption of water and solutes

  • regulation of blood pH by selectively reabsorbing certain ions

the loop of Henle

• U-shaped tubule within kidney nephron

• starts in the renal cortex and descends into the renal medulla

• comprises of two main sections:

  • ascending limb

  • descending limb

descending limb

• first section through which filtrate travels

• narrow

• highly permeable to water

• impermeable to ions

ascending limb

• second section, follows descending limb

• wider than descending limb

• impermeable to water

• permeable to ions

water reabsorption in the loop of Henle

1. In descending limb, water leaves filtrate via osmosis into interstitial space

2. filtrate loses water as it moves down descending limb-reaching lowest WP at tip in medulla

3. Lost water is reabsorbed into blood in surrounding capillaries and is carried away

4. ascending limb→ impermeable to water but permeable to Na⁺ and Cl^-

5. Na⁺ and Cl^- diffuse out of filtrate into interstitial space at bottom of ascending limb due to low WP

6. WP in interstitial space of medulla is is v. low

7. Na⁺ and Cl^- need to be actively transported out of top of ascending limb as WP increases as it ascends

8. water potential gradient created in interstitial→ highest WP in cortex and increasingly lower WP deeper into the medulla

what happens when filtrate enters collecting duct

1. water moves from filtrate in collecting duct into interstitial space and then into surrounding capillaries

2. water continues to exit filtrate as it moves through the collecting duct

3. urine leaving collecting duct has very low WP as most water has been reabsorbed into blood

countercurrent multiplier

• loop of Henle operates as a counter current multiplier system- intensifies salt gradient in medulla

• concentrates urine

• ensures there is always a WP gradient drawing water out of the collecting duct

• If flows were parallel, less reabsorption would occur

how is the countercurrent multiplier set up

1. as filtrate moves down collecting duct, it loses water→ decreases WP

2. due to pumping of ions out of ascending limb of loop of Henle, WP of surrounding tissues in medulla is even lower than in collecting duct

3. allows water to continue to move out of filtrate down whole length of collecting duct

ADH

antidiuretic hormone

key features of ADH

• produced in hypothalamus

• stored in posterior pituitary gland after production

• target cells are those lining DCTs and collecting ducts in kidneys

mechanism of ADH action

1. ADH attaches to receptors on surface of cells in DCT and collecting duct

2. Triggers activation of cAMP→ second messenger that initiates cascade of reactions leading to phosphorylation of water channel proteins (aquaporins)

3. Aquaporin vesicles merge with cell surface membrane

4. water moves through aquaporins via osmosis from DCT and CD into surrounding interstitial space

5. water reabsorbed into surrounding blood vessels

response to lack of water

1. water moves from osmoreceptors into blood→ osmoreceptors shrink, detecting decrease in WP of blood. Respond by producing ADH

2. Nerve signals prompt release of ADH from posterior PG and ADH transported via blood to the kidneys

3. increase in aquaporins in DCT and CD cell membranes= greater permeability to water

4. More water reabsorbed into the blood

5. urine becomes more concentrated and is produced in smaller volumes

response to excess water

1. water moves into osmoreceptors from blood via osmosis and osmoreceptors detect an increase in WP of blood

2. nerve signals to posterior PG decrease, reducing release of ADH

3. DCT and collecting duct cell membranes become less permeable to water

4. less water reabsorbed into the blood

5. urine becomes more dilute and is produced in larger volumes

use of urine samples for medical diagnosis

key indicators of medical conditions found in urine:

• presence of glucose can indicate diabetes

• elevated creatinine in urine= muscle and/ or kidney damage

• presence of blood/ proteins in urine may signal kidney disorders

use of urine samples for pregnancy testing

• hCG is a hormone produced by placenta after embryo is implanted in uterus

• presence of hCG in blood or urine indicates pregnancy

• Modern pregnancy tests use monoclonal antibodies that specifically target hCG

how do pregnancy tests work

1. wick of test soaked in urine

2. mobile monoclonal antibodies with coloured beads bind to hCG to form antibody-hCG complex

3. urine carries complex to window with immobilised monoclonal antibodies that bind to antibody-hCG complex

4. creates a coloured line/ symbol, indicating pregnancy

5. other immobilised antibodies bind to mobile antibodies with or without hCG, forming control line to confirm test is working

the use of urine samples for drug detection

• drugs filtered through the kidneys and are removed during urination→ urine typically contains evidence of drugs a person has used

• E.g.:

  • anabolic steroids can be used illegally by athletes

  • illegal recreational drugs e.g. cocaine can be tested for in urine samples

how to urine drug tests work

1. carry out an immunoassay-. monoclonal antibodies bind to drug or its breakdown product to indicate whether urine sample contains them

2. vaporise urine sample with known solvent

3. separate components of sample using gas chromatography

4. use mass spec. to identify molecular structures in the sample.

causes of kidney failure

• occurs when kidneys are unable to function effectively→ cannot filter blood and eliminate waste products properly

• Two main causes:

  • Kidney infections→ lead to inflammation and swelling in the kidneys, damaging cells responsible for filtering and reabsorption

  • High blood pressure→ can damage glomeruli capillaries so proteins and blood leak into urine

indicators of kidney failure

• Glomerular filtration rate (GFR)→ measure of how much blood is filtered in Bowman’s capsules of the nephrons

• used as an indicator of kidney failure:

  • low GFR= less effective blood filtration

  • blood test can measure level of creatinine in blood→ used to estimate GFR

  • high level of creatinine signals that kidneys are not working properly and could indicate kidney disease

effects of kidney failure

• build-up of mineral ions in blood→ electrolyte and osmotic imbalances

• build up of toxic urea in blood→ can poison cells

• high blood pressure→ may cause heart problems and strokes

• loss of calcium and phosphorus balance→ weakens bones

• build up of abnormal proteins in blood→ causes pain and joint stiffness

• anaemia→ causes tiredness and lethargy

how does dialysis filter the blood

1. patient’s blood passes along one side of a semi-permeable membrane

2. dialysis fluid contains normal plasma levels of mineral ions→ ions diffuse through dialysis tubing membrane into blood until normal ion levels

3. dialysis fluid has normal plasma levels of glucose→ glucose diffuses from fluid to blood until equal conc. reached

4. dialysis fluid has no urea→ urea diffuses into fluid from blood

5. larger molecules remain in blood→ cannot pas through membrane

types of renal dialysis

• haemodialysis:

  • blood leaves patients body and flows into dialysis machine

  • blood filtered in dialysis machine and returned to body

• peritoneal dialysis:

  • peritoneum→ membrane lining abdominal cavity

  • acts as surface across which substances exchanged between blood and dialysis fluid

  • dialysis fluid injected into and then drained from abdominal cavity so blood can be filtered within body itself

advantages and disadvantages of peritoneal dialysis

• advantages:

  • no need for specialist equipment

  • can be done at home by patient

  • patient can be mobile during treatment

• disadvantages:

  • risk of infection

  • required more frequently

advantages and disadvantages of haemodialysis

• advantages:

  • lower risk of infection

  • required less frequently

• disadvantages:

  • requires specialist equipment

  • must be done in hospital or medical centre

  • patient must be immobile during treatment

advantages of kidney transplants

• no need for regular dialysis sessions

• no need for dietary monitoring

• prevents build up of waste products between dialysis sessions that cause long term damage

• generally improves quality of life

• one of cost rather than several long-term payments in dialysis

disadvantages of kidney transplants

• risk of organ rejection if immune system recognises antigens as foreign and attacks

• shortage of donor kidneys

• necessitates use of medication to suppress immune system

• involves associated risks of surgery